Issues in applying recent CPMP ‘Points to Consider’ and FDA guidance documents with biostatistical implications

The International Conference on Harmonisation guideline ‘Statistical Principles for Clinical Trials’ was adopted by the Committee for Proprietary Medicinal Products (CPMP) in March 1998, and consequently is operational in Europe. Since then more detailed guidance on selected topics has been issued by the CPMP in the form of ‘Points to Consider’ documents. The intent of these was to give guidance particularly to non‐statistical reviewers within regulatory authorities, although of course they also provide a good source of information for pharmaceutical industry statisticians. In addition, the Food and Drug Administration has recently issued a draft guideline on data monitoring committees. In November 2002 a one‐day discussion forum was held in London by Statisticians in the Pharmaceutical Industry (PSI). The aim of the meeting was to discuss how statisticians were responding to some of the issues covered in these new guidelines, and to document consensus views where they existed. The forum was attended by industry, academic and regulatory statisticians. This paper outlines the questions raised, resulting discussions and consensus views reached. It is clear from the guidelines and discussions at the workshop that the statistical analysis strategy must be planned during the design phase of a clinical trial and carefully documented. Once the study is complete the analysis strategy should be thoughtfully executed and the findings reported. Copyright © 2003 John Wiley & Sons, Ltd.     

Missing item imputation for quality-of-life instruments with application to asthma quality-of-life questionnaires

There has been increasing use of quality-of-life (QoL) instruments in drug development. Missing item values often occur in QoL data. A common approach to solve this problem is to impute the missing values before scoring. Several imputation procedures, such as imputing with the most correlated item and imputing with a row/column model or an item response model, have been proposed. We examine these procedures using data from two clinical trials, in which the original asthma quality-of-life questionnaire (AQLQ) and the miniAQLQ were used. We propose two modifications to existing procedures: truncating the imputed values to eliminate outliers and using the proportional odds model as the item response model for imputation. We also propose a novel imputation method based on a semi-parametric beta regression so that the imputed value is always in the correct range and illustrate how this approach can easily be implemented in commonly used statistical software. To compare these approaches, we deleted 5% of item values in the data according to three different missingness mechanisms, imputed them using these approaches and compared the imputed values with the true values. Our comparison showed that the row/column-model-based imputation with truncation generally performed better, whereas our new approach had better performance under a number scenarios.     

欧洲主权债务危机:起因、演进、治理

阐述了目前在欧洲两种治理债务危机的思路发生的激烈碰撞;其中以“紧缩换援助”的治理债务危机思路遭到许多经济学家的质疑和希腊等重灾国的激烈反对,以促进结构改革和经济增长来摆脱欧债危机的主张正在获得越来越多的支持;指出欧盟必须适时转变治理危机的思路,并从五个方面提出治理危机的措施,尝试为欧债危机的解决找到出路.     

Am I a leader? Examining leader identity development over time

The extent to which someone thinks of him- or herself as a leader (i.e., leader identity) is subject to change in a dynamic manner because of experience and structured intervention, but is rarely studied as such. In this study, we map the trajectories of leader identity development over a course of a seven-week leader development program. Drawing upon identity theory (Kegan, 1983) and self-perception theory (Bem, 1972), we propose that changes in self-perceived leadership skills are associated with changes in leader identity. Using latent growth curve modeling and latent change score analyses as our primary analytical approaches, we analyzed longitudinal data across seven measurement points (N = 98). We find leader identity to develop in a J-shaped pattern. As hypothesized, we find that these changes in leader identity are associated with, and potentially shaped by, changes in leadership skills across time.     

Skill utilization and well-being: a cross-level story of day-to-day fluctuations and personal intrinsic values

The opportunity to use one's skills at work is an important prerequisite for employee well-being. Drawing on self-determination and person-environment fit theory, this diary study aims to add to our understanding of this important phenomenon in two ways. Firstly, we examine the associations of within-subject daily variations in skill utilization with well-being. Secondly, we model work value orientation as a between-subject factor that moderates this within-subject relationship. Specifically, we advocate that daily skill utilization is more beneficial (in terms of more daily work engagement and less daily emotional exhaustion) for employees holding predominantly intrinsic (i.e. self-development, community contribution) as opposed to extrinsic (i.e. financial success, status) values. Results of multilevel modelling using diary data from 99 service workers over five working days, supported the assumption that daily skill utilization was positively related to daily work engagement, particularly among employees holding a predominantly intrinsic work value orientation. Contrary to our expectations, daily skill utilization was unrelated to daily exhaustion, both for employees holding high and low intrinsic values. The discussion highlights the importance of, and employees’ receptiveness to, variations in beneficial working conditions.     

论非同一物——阿多诺的辩证法

阿多诺写作风格上的矛盾实质上是哲学思想本身的矛盾.阿多诺哲学的核心是对概念的同一性的内在否定,这只有在近代以来的理性批判传统中才能被适当理解.阿多诺对概念的意义史的解构,展示出作为概念之他者的非同一物,并借助同一性与非同一物的差异性,表达一种新型的同一性:星丛.否定辩证法的这一运作是直接来自于黑格尔辩证法的内在批判,最早可以追溯到柏拉图的辩证法.